评估侵袭性尿道膀胱癌（BCa）接受根治性膀胱切除术（RC）的患者中不同组织学亚型（VHs）对疾病特异性生存率（DSS）的影响。我们分析了8个中心的1082名接受upfront RC治疗cT1-4aN0M0尿道内皮BCa的多机构队列。单变量和多变量Cox回归分析用于评估不同VHs对总体队列和三个基于阶段的分析中DSS的影响。这些阶段被定义为“器官内限”（≤pT2N0）、“局部晚期”（pT3-4N0）和“淋巴结阳性”（pTanyN1-3）。总体而言，784名患者（72.5％）患有单纯的尿道上皮癌（UC），其余298名（27.5％）患有VH。鳞状分化是最常见的VH，在166名患者（15.3％）中观察到，其次是微小乳头状（40名患者[3.7％]）、肉瘤性（29名患者[2.7％]）、腺样（18名患者[1.7％]）、淋巴上皮瘤状（14名患者[1.3％]）、小细胞（13名患者[1.2％]）、透明细胞（8名患者[0.7％]）、嵌套（7名患者[0.6％]）和浆细胞样VH（3名患者[0.3％]）。中位随访时间为2.3年。总体而言，发生了534例（49.4％）与疾病相关的死亡。在单变量和多变量分析中，浆细胞和小细胞VH与总体队列中更差的DSS相关（P = 0.04）。在单变量分析中，肉瘤性VH与更差的DSS显著相关，而淋巴上皮瘤状VH相对于纯UC具有有利的DSS。在器官内限和淋巴结阳性队列中，透明细胞（P = 0.015）和小细胞（P = 0.011）VH分别与更差的DSS相关。超过25％的患者在膀胱切除术时患有VH。与纯UC相比，透明细胞、浆细胞、小细胞和肉瘤性VH与更差的DSS相关，而淋巴上皮瘤状VH具有DSS益处。准确的VH病理诊断可能确保个性化咨询，以确定需要更密集治疗的患者。©2023年BJU International。

To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC).We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as 'organ-confined' (≤pT2N0), 'locally advanced' (pT3-4N0) and 'node-positive' (pTanyN1-3).Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable DSS compared to pure UC. Clear-cell (P = 0.015) and small-cell (P = 0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively.More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.© 2023 BJU International.